The Distinct Metabolic Phenotype of Lung Squamous Cell Carcinoma Defines Selective Vulnerability to Glycolytic Inhibition

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dc.contributor.authorGoodwin, Justinen_US
dc.contributor.authorNeugent, Michael L.en_US
dc.contributor.authorLee, Shin Yupen_US
dc.contributor.authorChoe, Joshua H.en_US
dc.contributor.authorChoi, Hyunsungen_US
dc.contributor.authorJenkins, Dana M. R.en_US
dc.contributor.authorRuthenborg, Robin J.en_US
dc.contributor.authorRobinson, Maddox W.en_US
dc.contributor.authorJeong, Ji Yunen_US
dc.contributor.authorWake, Masakien_US
dc.contributor.authorAbe, Hajimeen_US
dc.contributor.authorTakeda, Norihikoen_US
dc.contributor.authorEndo, Hirokoen_US
dc.contributor.authorInoue, Masahiroen_US
dc.contributor.authorXuan, Zhenyuen_US
dc.contributor.authorYoo, Hyuntaeen_US
dc.contributor.authorChen, Minen_US
dc.contributor.authorAhn, Jung-Moen_US
dc.contributor.authorXuan, Zhenyuen_US
dc.contributor.authorYoo, Hyuntaeen_US
dc.contributor.authorChen, Minen_US
dc.contributor.authorAhn, Jung-Moen_US
dc.contributor.authorMinna, John D.en_US
dc.contributor.authorHelke, Kristi L.en_US
dc.contributor.authorSingh, Pankaj K.en_US
dc.contributor.authorShackelford, David B.en_US
dc.contributor.authorKim, Jung-whanen_US
dc.contributor.utdAuthorGoodwin, Justinen_US
dc.contributor.utdAuthorNeugent, Michael L.en_US
dc.contributor.utdAuthorLee, Shin Yupen_US
dc.contributor.utdAuthorChoe, Joshua H.en_US
dc.contributor.utdAuthorChoi, Hyunsungen_US
dc.contributor.utdAuthorJenkins, Dana M. R.en_US
dc.contributor.utdAuthorRuthenborg, Robin J.en_US
dc.contributor.utdAuthorRobinson, Maddox W.en_US
dc.contributor.utdAuthorXuan, Zhenyuen_US
dc.contributor.utdAuthorYoo, Hyuntaeen_US
dc.contributor.utdAuthorKim, Jung-whanen_US
dc.date.accessioned2018-08-20T16:31:43Z
dc.date.available2018-08-20T16:31:43Z
dc.date.created2017-05-26en_US
dc.date.issued2018-08-20
dc.descriptionIncludes supplementary materialen_US
dc.description.abstractAdenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high F-18-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient.en_US
dc.description.departmentSchool of Natural Sciences and Mathematicsen_US
dc.description.sponsorship"This work was supported by the UT Dallas start-up fund and American Lung Association LCD-400239 (J.-w.K.), NIH R01 CA163649 and SPORE 2P50 CA127207 (P.K.S.), NIH K25 AR063761 (M.C.), Project for Development of Innovative Research on Cancer Therapeutics, Japan Agency for Medical Research and Development, JSPS Kakenhi JP26111005 and Takeda Science Foundation (M.I.), JP25461937 (H.E.), Grant-in-Aid for Scientific Research on Promotion of Science, 16K09493, on Innovative Areas, 26111003, JST PRESTO, the Banyu Life Science Foundation International and Takeda Science Foundation (N.T.), Welch Foundation, AT-1595 (J.-M.A.), NIH, NCI P50CA70907 (SPORE), Cancer Prevention and Research Institute of Texas (CPRIT) RP110708 (J.D.M.)."en_US
dc.identifier.bibliographicCitationGoodwin, Justin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, et al. 2017. "The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition." Nature Communications 8(15503), doi:10.1038/ncomms15503en_US
dc.identifier.issn2041-1723en_US
dc.identifier.issue15503en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/5999
dc.identifier.volume8en_US
dc.publisherSpringer Natureen_US
dc.relation.urihttp://dx.doi.org/10.1038/ncomms15503
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2017 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceNature Communications
dc.subjectMessenger RNAen_US
dc.subjectGlucoseen_US
dc.subjectLungs—Canceren_US
dc.subjectSquamous cell carcinomaen_US
dc.subjectGlucose Transporter Type 1en_US
dc.subjectAdenocarcinomaen_US
dc.subjectTumorsen_US
dc.subjectCancer—Treatmenten_US
dc.subjectCarcinoma, Non-Small-Cell Lungen_US
dc.titleThe Distinct Metabolic Phenotype of Lung Squamous Cell Carcinoma Defines Selective Vulnerability to Glycolytic Inhibitionen_US
dc.type.genrearticleen_US

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